The present study will attempt to determine whether defective maturation of 45S rRNA is an early event during hepatocarcinogenesis and a prerequisite for neoplastic transformation. Previous studies indicate that there are aberrations in the post-transcriptional stability of newly formed rRNA in cells undergoing neoplastic transformation following the administration of chemical carcinogens. Very little information is available concerning the mechanisms accounting for decreased RNA stability. We will investigate defects in maturation of ribosomal RNA in male rats fed a diet containing the hepatocarcinogen, aflatoxin B1 or 3'-methyl-4-dimethylaminoazobenzene (3'-Me-DAB). Rats will be sacrificed at intervals of 2, 4, 6, 12, 24 and 36 weeks. Control rats will be fed identical diets (nutritionally deficient) but lacking the carcinogen and/or nutritionally balanced diets. We want to test whether these two different carcinogens induce the same types of defect in the processing and transport of 45S precursor RNA. In studying the fate of 45S rRNA in the various tissues we will examine the following parameters: a) in vitro stability of 45S rRNA and cytoplasmic rRNA; b) the degree of in vivo methylation of 45S rRNA; c) the activity of the nucleolar methyl transferases; d) the activity of nuclear and cell sap alkaline RNase and RNase inhibitor; and e) the activity of nucleolar RNA polymerase. This study will determine whether deranged rRNA metabolism occurring initially in normal liver cells of rats fed potent hepatocarcinogens is a primary cause of progressive irreversible biochemical alterations leading to neoplasia.